Global Vaccine Safety

Safety of live 14-14-2 Japanese encephalitis vaccine

Extract from report of GACVS meeting of 12-13 December 2007, published in the WHO Weekly Epidemiological Record on 25 January 2008

GACVS reviewed an updated report on the frequency and severity of AEFI reported with the use of live Japanese encephalitis vaccine (JEV) in the Republic of Korea, where it was introduced in 2002 but is used only in the private sector. The recommended schedule is 2 doses administered 12 months apart in children aged 1–2 years and a booster at 6 years of age. Inactivated mouse-brain JEV is used in the national immunization programme. Since the private sector is not linked to AEFI surveillance, no safety data are available on the >1.7 million doses of live JEV distributed since 2002. The national requirement for the introduction of new drugs is to investigate adverse events in detail in 600 subjects. Among 673 children followed up after a dose of live JEV, 318 events were reported in 163 subjects; most AEFI reported were relatively minor, non-neurological and indistinguishable from common childhood illnesses. The review of the safety of live JEV will be finalized in 2008.

GACVS also reviewed a study on co-administration of measles vaccine (MV) with live JEV conducted in the Philippines. Three groups of 223–228 infants (aged 9–11 months) were given either JEV followed by MV a month later, MV followed by JEV a month later or both given simultaneously. The design was to examine non-inferiority of response to MV when co-administered. One month after vaccination, although overall sero-protection was very high in all 3 groups, in the group in which the vaccines were co-administered, the proportion of infants who achieved sero-protection following MV (96%) was slightly lower than in the MV-only group (100%); [difference = –4%, 95% confidence interval, –1, –6]). In addition, the antibody titres were significantly lower in the co-administration group than in those who had received only MV.

These results indicate some interference of live JEV on MV response. Among those who had sero-converted by 1 month, at 1-year follow-up the geometric mean antibody titres were similar in both groups, suggesting that the interference is only temporary and that co-administration of live JEV and MV is acceptable.

Based on earlier reviews and the information from the above studies, GACVS concluded that the short-term safety profile of live JEV appears satisfactory and the vaccine could safely be administered with measles vaccine as of 9 months of age. More investigations are needed to confirm that low-frequency adverse events (especially neurological) do not occur. Since live JEV is currently used in “catch-up” campaigns on many millions of children in Asian countries, the opportunity should be taken to examine if the vaccine-safety profile remains valid in large study populations. Further studies to check if MV effectiveness remains undiminished should be encouraged.